International Patent Application Publication No. WO 2005/012266 discloses carbamoyl-cyclohexane derivatives that are D3 and D2 dopamine receptor subtype preferring ligands. WO 2005/012266 discloses that trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl)}-3,3-dimethyl-urea has a binding affinity for dopamine D3 receptors (IC50 between 1 and 10 nM) and a binding affinity for dopamine D2 receptors (IC50 between 10 and 50 nM). Thus, trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl-urea may be used as a mixed dopamine D3/D2 receptor ligand for use in the treatment of disorders which require modulation of dopamine receptor(s).
One particular carbamoyl-cyclohexane derivative disclosed in Hungarian Patent Application No. P0700339 and U.S. Pat. No. 7,737,142 is trans-4-{2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexylamine hydrochloride, which is also known as trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl-urea hydrochloride, or cariprazine, the structural formula for which is shown below in figure (I).

Hungarian Patent Application No. P0700339 also discloses processes for preparing trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl-urea hydrochloride, and describes a crystalline form of trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl-urea hydrochloride, which will be referred to hereinafter as polymorph “Form I”. The crystalline hydrochloride salt of polymorph Form I is disclosed in U.S. Pat. No. 7,943,621, as well as solvates and hydrates thereof.
U.S. Pat. No. 7,829,569 discloses processes for preparing trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl-urea hydrochloride, and describes a crystalline form of trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl-urea hydrochloride, which will be referred to hereinafter as polymorph “Form III”.
Pharmaceutical co-crystals are crystalline molecular complexes that contain the drug substance along with an additional molecule present in the same crystal structure. The additional molecule or guest has been described in the literature as a co-crystal former. Co-crystalline forms show different physicochemical properties compared to the drug substance alone, including melting point, chemical reactivity, apparent solubility, dissolution rate, optical and mechanical properties, vapor pressure, and density. These properties can have a direct effect on the ability to process and/or manufacture a drug substance and the corresponding finalized dosage forms, as well as an effect on drug product stability, dissolution, and bioavailability. Co-crystallization has also been used to isolate or purify a drug substance during manufacturing.
Co-crystal formation and the properties of co-crystalline forms cannot be predicted on the basis of known properties of the drug substance and the co-crystal former. Disclosed herein are novel co-crystals of trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl-urea hydrochloride and an acid, e.g., fumaric acid and oxalic acid.